What Is Osteoporosis?

Our bones are composed of complex living tissues that together are responsible for protecting vital internal organs, supporting our muscles, and storing minerals such as calcium.  Throughout our lives, older bone tissue is constantly being removed and replaced with new bone tissue in a process termed bone remodeling.  In children and young adults, this process is responsible for generating large amounts of new bone tissue.  In older adults, the remodeling process is essential to regulate calcium levels and repair damaged tissue.  It is estimated that approximately 10% of adult bone tissue is replaced every year.


By the time we reach 30, we have achieved our ‘peak bone mass,’ meaning that our bones are at their maximum strength and density levels.  During advanced adulthood, bone tissue is generally removed faster than it is replaced leading to decreased bone density.  The disease osteoporosis is defined as a decrease in bone strength and density along with a simultaneous increased risk for bone fractures.  Osteoporosis affects women and men of all races and ethnic groups, though it is five times more likely to develop in women than men.  Given that bone loss is exacerbated by a reduction in estrogen levels produced after menopause, most women tend to lose bone tissue rapidly in the first 4 to 8 years after menopause.  However, approximately 20% of all men also demonstrate an age-related loss in bone tissue.


Environmental risk factors for Osteoporosis

It was previously believed that osteoporosis was a natural and unavoidable part of aging. In the United States alone, more than 40 million people either already have osteoporosis or are at high risk due to low bone mass.  This disease often leads to bone fractures of the hip, spine, and wrist, which can quickly alter our overall quality of life.  It has even been estimated that up to one half of all women and one quarter of all men 50 years of age and older will experience a hip fracture during their lifetime.  Recent medical advances now assert that osteoporosis is a largely preventable disease. Reliable prediction of who is most likely to suffer from bone fractures will aid in prevention and keep aging individuals healthy.


Only 50% of risk is attributable to genetics

Recent studies estimate that 50% of your risk for osteoporosis is caused by genetic factors while the other 50% is caused by non-genetic environmental factors.  Some of these environmental factors are:

  • Increasing age
  • Gender, based on if you will experience menopause
  • Amenorrhea in women
  • Low testosterone levels in men
  • Lifelong low calcium intake
  • Low body weight (BMI)
  • Having experienced a bone fracture at 50 or older
  • Excessive alcohol or tobacco use
  • Inadequate physical exercise
  • Specific endocrine disorders or chronic diseases of the lungs, kidneys, stomach, and intestines
  • Prolonged use of certain medications such as steroids, antacids, anticonvulsants

While some of these risk factors can be managed or altered, others cannot be changed.  Thus, in order to proactively manage our health as we age, we should access our levels of both non-genetic and genetic risk factors for osteoporosis.


Multiple Genes Are Associated With Osteoporosis

A plethora of data from family histories, analyses of twins, and large genetic investigations has determined that osteoporosis is partially an inherited polygenic disease- meaning it is influenced by multiple genes (i.e. specific pieces of DNA) that are passed to us from our parents.  Many of these studies have analyzed the association between bone mineral density (BMD), risk of bone fractures, and specific gene regions.  One of the largest BMD genetic studies was from the International Genetic Factors of Osteoporosis Consortium which analyzed 32,000 individuals from 17 different populations and then reassessed its initial findings in another 50,000 individuals. In this study, multiple DNA regions were significantly associated with BMD, and 14 of these regions were also associated with an increased fracture risk.

In a study with similar success, a European Commission along with several US institutes, such as the National Institute on Aging (NIA) and National Institute for Arthritis, Musculoskeletal and Skin Diseases (NIAMS) analyzed 80,000 people across North America, Europe, East Asia and Australia to discover genes associated with bone mineral density.  Now it is up to scientists to look at these individual regions of DNA and determine if any individual DNA differences are useful in predicting our chances of developing osteoporosis.  Recent data has already suggested that this fact is true: below are two genes that are currently being analyzed for their association with osteoporosis.

The COL1A1 gene (collagen, type I, alpha 1) produces a long fibrous structural protein.  This type of collagen protein is abundant in bone tissue and is responsible for maintaining bone strength and structure. Multiple mutations in and around the DNA region producing this protein lead to the formation of abnormal bone strength and architecture.  One specific mutation near COL1A1 is associated with a 2–4-fold increased risk of bone fracture.  Other studies have also correlated this same mutation with low bone density.  Mutations in this gene were previously correlated with severe defects in connective tissue at birth leading to brittle bones throughout life.

The LRP5 gene (low density lipoprotein receptor-related protein 5) produces a protein that is localized in the outer membrane of many types of cells. This protein can participate in many cellular signaling pathways, such as pathways required to promote tissue development.  This protein has been demonstrated to be involved in the regulation of bone mineral density and is known to be mutated in more serious forms of osteoporosis that develop in infants and juveniles.  Multiple mutations throughout the gene have been associated with changes in BMD and bone fracture risks.


Who Should Be Tested For Genetic Mutations Associated With Osteoporosis?

One of the main issues with osteoporosis management is our ability to diagnose exactly who is at risk to develop a bone fracture before it happens.  Current medical guidelines utilize bone mineral density (BMD) testing to definitively diagnose osteoporosis and to detect low bone mass before osteoporosis develops in women who are 65 or older.

The most widely recognized test for measuring bone mineral density is a quick and painless noninvasive technology known as dual-energy x-ray absorptiometry (DEXA). This type of testing alone, however, is not able to accurately predict if you will suffer from future bone fractures.  Part of the problem is that disruption of the complex architecture of bone tissue may play a more significant role in bone fractures than previously thought.  Currently, many medical providers are using DEXA data plus self-reported information of non-genetic factors to assess an individual’s potential for bone fracture.  The FRAX® tool has also been developed by the World Health Organization (WHO) to evaluate the fracture risk of patients between the ages of 40 and 90 if they have participated in a DXA scan.

Though still in its infancy, private companies are now offering direct to consumer genetic testing for personal DNA changes associated with osteoporosis.  Most of these molecular tests look specifically at DNA regions associated with the COL1A1 and LRP5 genes.  While there are no current medical guidelines for osteoporosis genetic testing, both COL1A1 and LRP5 are known to be mutated in other severe diseases of the bone tissue.  Individuals with a strong family history of osteoporosis, a personal history of bone fractures, or radiographic findings of extremely low bone density may want to consider genetic testing.  As always, consulting with your family physician is advised when making important decisions about your health.


Taking Action If You Have Genetic Changes Associated With An Increased Osteoporosis Risk

Both DMX screening and genetic testing can only predict your likelihood of fracturing a bone.  But there are plenty of preventative steps you can take if your genetics predicts that you are at an increased risk for osteoporosis.  In order to lower your risk, the WHO recommends the following actions:

  • a physically active lifestyle, with some time regularly spent outdoors
  • a balanced diet providing a calcium intake of at least 800-1500 milligram per day
  • avoiding smoking and high alcohol consumption


Many medical practitioners also recommend adding a sufficient amount of vitamin K to your diet as well.  Vitamins D and K are essential for minimizing bone loss and maintaining overall health.  In addition, fall prevention is a critical concern for individuals with an increased bone fracture risk.  As we age, we should remember to regularly monitor our eyesight and eliminate home hazards such as cords, slippery surfaces, and poor lighting.  Finally, many physicians suggest establishing a baseline BMD through early testing.

How Can Genetic Testing Affect Your Total Health?

If you’re taking a proactive role in your bone health, then completing an early DMX screening after menopause and genetic testing should be on your to-do list.  Likewise, knowing your family history with regard to osteoporosis may help you decide how aggressive to be in your monitoring of this disease.  While you can’t change your genes, there are plenty of other risk factors you can alter for better health.  Overall, your quality of life doesn’t have to diminish as you age if you assume responsibility for your personal health.

Websites you can visit for additional information:

National Institute of Health’s Osteoporosis Health Publication


National Osteoporosis Society


World Health Organization (WHO) FRAX Tool for Risk Assessment


Fall Prevention Advice




Das S, Crockett JC. Osteoporosis – a current view of pharmacological prevention and treatment. Drug Des Devel Ther. 2013;7:435-48.

Estrada K, Styrkarsdottir U, Evangelou E, et al. Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nat Genet. 2012;44:491–501.

Flicker L, Hopper JL, Rodgers L, Kaymakci B, Green RM, Wark JD. Bone density determinants in elderly women: a twin study. J Bone Miner Res. 1995;10:1607-13.

McGuigan FE, Armbrecht G, Smith R, Felsenberg D, Reid DM, Ralston SH. Prediction of osteoporotic fractures by bone densitometry and COLIA1 genotyping: a prospective, population-based study in men and women. Osteoporos Int. 2001;12:91-6.

Mitchell BD, Streeten EA. Clinical impact of recent genetic discoveries in osteoporosis. Appl Clin Genet. 2013;6:75-85.

Styrkarsdottir U, Halldorsson BV, Gretarsdottir S, Gudbjartsson DF, Walters GB, Ingvarsson T, Jonsdottir T, Saemundsdottir J, Center JR, Nguyen TV, Bagger Y, Gulcher JR, Eisman JA, Christiansen C, Sigurdsson G, Kong A, Thorsteinsdottir U, Stefansson K. Multiple genetic loci for bone mineral density and fractures. N Engl J Med. 2008;358:2355-65.

Van Meurs JB, Trikalinos TA, Ralston SH, et al. GENOMOS Study. Large-scale analysis of association between LRP5 and LRP6 variants and osteoporosis. JAMA. 2008;299:1277-90.


Last Reviewed: 02-Feb-2014

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Michelle Thiaville PhD

Michelle Thiaville is a research scientist who is interested in the connections between personal genetics, nutrition, and cancer. She has published multiple articles in prominent scientific journals detailing her findings.